Ginsenoside Rg3 alleviates brain damage caused by chlorpyrifos exposure by targeting and regulating the...

The utilization of organophosphorus pesticides (OPs) has been demonstrated to exert a substantial positive influence on crop yield enhancement. However, due to the multitude of exposure routes and the persistence of these compounds, humans are routinely exposed to pesticides on a daily basis through dermal contact, inhalation, and ingestion. This has serious consequences for the health of living organisms. The existing research on the effects of organophosphorus pesticides on organisms primarily encompasses the impact on vital organs such as the liver, kidneys, heart, various blood parameters, and potential neurotoxicity, teratogenicity, carcinogenicity, and mutagenic effects. However, there is a paucity of research addressing the alleviation of brain tissue damage in OP pesticide poisoning through the microbial-intestinal-brain axis.

The objective of the present study is to illuminate the biological activity and mechanism of ginsenoside Rg3 in addressing brain injury induced by chlorpyrifos, employing both in vivo and in vitro models. This investigation will elucidate the role of the microbiota-gut-brain axis and the polarization of macrophages in this process.

Ginsenoside Rg3 is characterized by notable antioxidant and neuroprotective properties. The results showed that Rg3 improved the cognitive and learning memory impairment after chlorpyrifos (CPF) exposure in C57 mice, alleviated macrophage infiltration in the hippocampus, repaired synaptic ultrastructural damage and restored the absence of synapse-related proteins (BDNF, SYP, and PSD-95) through behavioral assays, ameliorated neuronal apoptosis and hypothalamo-pituitary-adrenal axis (HPA axis) disorders, and mediated the development of MPA axis disorders, while mediating M1/M2 macrophage polarization and attenuating apoptosis in brain tissue. In intestinal tissues, Rg3 improved the intestinal flora of mice, significantly reduced macrophage infiltration, and down-regulated the expression of pro-inflammatory cytokines (tumor necrosis factor-α, IL-1β, and IL-6), while concurrently augmenting the levels of short-chain fatty acids. And the therapeutic role of Rg3 in ameliorating the brain damage induced by chlorpyrifos exposure was substantiated by protein imprinting through the NLRP3/Caspase-1/IL-1β signaling pathway. Meanwhile, the results of in vitro experiments demonstrated that ginsenoside Rg3 could attenuate CPF-induced inflammatory responses in BV-2 microglia by modulating M1/M2 macrophage polarization.

The results of this study confirmed that ginsenoside Rg3 can be utilized as a promising therapeutic strategy to mitigate brain tissue damage resulting from OP-type pesticide poisoning. These findings suggest that Rg3 has the potential to serve as a promising clinical drug for the treatment of organs affected by organophosphorus pesticide poisoning. This study offers novel insights into the application of Rg3 in the context of the microbial-gut-brain axis, providing a theoretical foundation for the development of ginsenoside Rg3 in clinical settings and the future development of novel drugs.